The Apicomplexa are an eukaryotic protozoan phylum of around 5000 species including parasites which belong to the most successful and devastating pathogens today, infecting a wide range of animals from mollusks to mammals. Many species of Apicomplexa cause diseases of medical and veterinary importance and represent a significant economic burden and global healthcare challenge. Members of the phylum include:                Plasmodium, the etiological agent of malaria, afflicting 10-40% of world population and accounting for one-in-five deaths among children under the age of five in Africa        Toxoplasma gondii, the causative agent of toxoplasmosis. From one-third to half of the world's human population is estimated to carry a Toxoplasma infection. It is a major pathogen to humans with a weakened immune system, such as AIDS patients or pregnant women        Cryptosporidium, a waterborne pathogen which typically does not cause serious illness in healthy people, but is a big health problem for immuno-compromised people, and        the agricultural parasites Eimeria (infects poultry and causes annual losses in revenue totaling nearly a billion dollars), Neospora (an important pathogen in cattle and dogs),        
Babesia (thought to be the second most common blood parasites of mammals with a major health impact on domestic animals) and Theileria (causative agent of theileriosis a disease of cattle, sheep and goats).
The apicomplexan life cycle is complex and can be divided into three main stages wherein the first two serve for the asexual replication of the pathogen (more precise of the invasive stages of these protists called sporozoites and merozoites) and the third stage defines the sexual reproduction of the parasite. While the general life cycle is common to the Apicomplexa phylum, there are striking differences between species.
FIG. 1 shows the apicomplexan life cycles. As mentioned above, the members of Apicomplexa share a generalized life cycle, even though each species has its own specializations. Plasmodium spp. and Theileria spp. are transmitted and undergo sexual recombination in an insect vector, the Anopheles mosquito and Rhipicephalus tick, respectively. Cryptosporidium is able to autoinfect its host; the oocyst can sporulate and excyst in the same host, maintaining the infection for months to years. The Coccidian parasites are represented in this figure by Toxoplasma, which is able to infect the majority of warm-blooded animals. The differentiation of Toxoplasma tachyzoites into gametocytes is triggered only when members of the cat family (Felidae) are infected (Wasmuth, Daub et al. 2009).
Some Apicomplexa require a single host (e.g. Cryptosporidium), whereas others are more complex, requiring sexual reproduction in the vector species for transmission (e.g. Theileria and Plasmodium; see FIG. 2).
Although members of the Apicomplexa infect different host and cell types, they have a similar number of defining organelles involved in host cell attachment, invasion, and the establishment of an intracellular parasitophorous vacuole within the host cell. The arsenal of organelles varies between species, but typically includes rhoptries, micronemes, and dense granules. To develop novel anti-parasitic compounds and increase the understanding of apicomplexan biology, several large-scale-sequencing projects were initiated and the availability of genomic data sets for 15 species opened the way for the identification of conserved protein families and their functions within the phylum and in the above-mentioned processes. Domain analysis also identified both the taxonomic distribution of apicomplexan domains as well as domain architectures specific to the Apicomplexa.
In contrast to bacterial pathogens, these apicomplexan parasites are eukaryotic and share many metabolic pathways with their animal hosts. This fact makes therapeutic target development extremely difficult—a drug that harms an apicomplexan parasite is also likely to harm its human host.
Malaria is a disease caused by infection with parasites of the phylum Apicomplexa protozoan, namely parasites of the genus Plasmodium, globally causing more than 200 million new infections and 700 thousand deaths every year. Malaria is especially a serious problem in Africa, where one in every five (20%) childhood deaths is due to the effects of the disease. An African child has on average between 1.6 and 5.4 episodes of malaria fever each year.
Malarial diseases in humans are caused by five species of the Plasmodium parasite: P. falciparum, P. vivax, P. ovale, P. malariae and P. knowlesi, wherein the most prevalent being P. falciparum and Plasmodium vivax. Malaria caused by P. falciparum (also called malignantor malaria, falciparum malaria or malaria tropica) is the most dangerous form of malaria, with the highest rates of complications and mortality. Almost all malarial deaths are caused by P. falciparum. 
Briefly, the plasmodial life cycle in man starts with the inoculation of a few sporozoites through the bite of an Anopheles mosquito. Within minutes, sporozoites invade the hepatocyte and start their development, multiplying by schizogony. In the case of P. vivax and P. ovale, some sporozoites may differentiate into hypnozoites, responsible for late relapses of the infection. After a period of 5-14 days—depending on the plasmodial species—schizonts develop into thousands of merozoites that are freed into the bloodstream and invade the red blood cells (RBCs). In the RBC, each merozoite develops into a trophozoite that matures and divides, generating a schizont that, after fully matured, gives rise to up to 32 merozoites within 42-72 h, depending on the plasmodial species. The merozoites, released into the bloodstream, will invade other RBC, maintaining the cycle. Some merozoites, after invading a RBC, develop into sexual forms—the male or female gametocytes which also enter the bloodstream after maturation and erythrocyte rupture. When a female Anopheles mosquito takes its blood meal and ingests the gametocytes, it will become infected. In the mosquito gut, the male gametocyte fuses with the female gametocyte, forming the ookinete, which binds to and passes through the gut wall, remains attached to its external face and transforms into the oocyst. The oocyst will divide by sporogony, giving rise to thousands of sporozoites that are released in the body cavity of the mosquito and eventually migrate to its salivary gland, where they will maturate, becoming capable of starting a new infection in humans when the mosquito bites the host for a blood meal.
Resistance of P. falciparum to the existing anti-malarial drug chloroquine emerged in the sixties and has been spreading since then. In addition, the malaria parasite has developed resistance to most other anti-malarial drugs over the past decades. This poses a major threat to public health in tropical countries and to travellers. There is every reason to believe that the prevalence and degree of anti-malarial drug resistance will continue to increase.
Therefore the availability of novel therapeutic strategies against malaria would be highly advantageous.